Connectivity analyses of bioenergetic changes in schizophrenia: Identification of novel treatments

Courtney R. Sullivan; Catharine A. Mielnik; Sinead M. O’Donovan; Adam J. Funk; Eduard Bentea; Erica A.K. DePasquale; Zhexing Wen; Vahram Haroutunian; Pavel Katsel; Amy J. Ramsey; Jarek Meller; Robert E. McCullumsmith

Pre-pulse inhibition of the acoustic startle response was measured on day 16, via SR-LAB equipment and software from San Diego Instruments (San Diego Instruments, San Diego, CA, USA). Accelerometers were calibrated to 700±5 mV and output voltages were amplified and analyzed for voltage changes using SR Analysis, and exported as an excel file. Background white noise was maintained at 65dB. PPI was measured in a 30-min test with 80 randomized trials of: (1) 10 trials pulse alone (2) 10 trials pre-pulse alone (for each pre-pulse), (3) 10 trials pre-pulse plus pulse (for each pre-pulse), and (4) 10 trials no pulse. 5 pulse alone trials were performed before and after the 80 trials, totaling 90 trials per run. The pre-pulse (4dB, 8dB, or 16dB) was presented 100ms prior to the startle pulse (165dB). The inter-stimulus interval (ISI) was randomized between 5 and 20s. Experimental mice were placed in a cylindrical tube on a platform in a soundproof chamber. Mice were allowed to acclimatize in the chamber and to the background noise for 300s, followed by 5 consecutive pulse alone trials, then by 80 randomized trials (as described above) and then 5 consecutive pulse alone trials. Pre-pulse inhibition was measured as a decrease in the amplitude of startle response to a 100dB acoustic startle pulse, following each pre-pulse (4dB, 8dB and 16dB).